The overall goal of this Program Project is to study the basic biology of signal hematopoietic cells as it relates to human disease status. Abnormalities in signal transduction can lead to diseases of hematopoietic cell overproduction (leukemia) or underproduction (cytopenias). There are two major signal transduction pathways defined in hematopoietic cells: the RAS/Raf/MAP kinase pathways and the JAK/STAT pathway that underlie hematopoietic disease. Project 2 will focus on the interaction between BCR/ABL and the CRKL adapter protein and its functional importance in the pathogenesis of stable phase CML. Project 3 will investigate the function of the phosphatase, SHPTP1, and its ability to associate with and down- modulate the CSF-1 Receptor and BCR/ABL signals. Project 4 will investigate the signal transduction mechanism of two newly-identified hematopoietic oncoproteins, Te1/PDGFR and Tel/ABL. An Administrative Core and an Animal Core 9001 are also outlined. Multiple interactions among the four projects are also delineated.